The goal of this component of the program project is to develop a plant- based production system for generating medically safe and affordable pharmaceutical grade monoclonal antibodies against (+)methamphetamine ((+)METH). While antibody therapy shows tremendous promise in the treatment of (+)METH overdose and addiction, the cost to produce these antibodies using current technologies is expected to prohibit their wide spread availability. The use a plant- based production system will reduce the cost of antibody production by at least 10 fold. We have proposed research that will lead to expression and purification of gram quantities of anti-(+)METH IgG from plans, which are designed to be immunologically silent in therapeutic applications. Experiments will then be conducted with IgG from plants and from bioreactor cultured hybridoma cells (provided by the Core) to characterize their in vitro structure and functional equivalence. These studies will include a characterization of antibody affinity for (+)METH, antibody size, the presence or absence of glycosylation, and antibody purity. Finally, this line of investigation will culminate with the production of a high-resolution structural model of antibody (for plant and bioreactor produced) bound to (+)METH. As suitable quantities become available, IgG from plants will be used in animal models of (+)METH abuse to examine its pharmacological bioequivalence. These studies will be conducted by personnel at the Core facility utilizing behavioral and pharmacokinetic measures developed by other components of the program project. The preclinical testing of plant- produced IgG by other components in the program project should provide the critical proof needed to progress to the next stage of preclinical or clinical trials of anti-(+)METH IgG form plants.